Medicine and Health Sciences Commons^™

Activation In Neural Networks Controlling Ingestive Behaviors: What Does It Mean, And How Do We Map And Measure It?, Alan Watts, Arshad Khan, Graciela Sanchez-Watts, Dawna Salter, Christina Neuner

Selected Works Temporary Series

No abstract provided.

Activation In Neural Networks Controlling Ingestive Behaviors: What Does It Mean, And How Do We Map And Measure It?, Watts, Arshad Khan, Graciela Sanchez-Watts, Dawna Salter, Christina Neuner

Departmental Papers (Biology)

No abstract provided.

Abdominal Pain With Rigidity Secondary To The Anti-Emetic Drug Metoclopramide, Nadeem Ullah Khan, Junaid A. Razzak

Department of Emergency Medicine

We report a case of abdominal pain with rigidity, mimicking an acute abdomen, caused by metoclopramide, a common anti-emetic drug. Extrapyramidal symptoms are commonly reported side-effects of this medication. They generally include involuntary movements of limbs, torticollis, oculogyric crisis, rhythmic protrusion of tongue, trismus, or dystonic reactions resembling tetanus, etc. Abdominal rigidity due to this medication, resembling an acute abdomen, has not been reported previously. This case report illustrates the importance of considering medication side-effects when evaluating a patient with abdominal pain and rigidity.

The Burden Of Anxiety And Depression Among Patients With Chronic Rheumatologic Disorders At A Tertiary Care Hospital Clinic In Karachi, Pakistan, Abdul Waheed, Kamran Hameed, Abdul Moiz Khan, Junaid Ali Syed, Ahmed Iqbal Mirza

Medical College Documents

Objectives: To study the burden of anxiety and depression as a comorbid among patients of chronic rheumatological disorders and to investigate possible determinants of depression and anxiety.Methods: It was a cross-sectional study conducted at the rheumatology clinic of The Aga Khan University Hospital (AKUH) Karachi, Pakistan. With convenient sampling, 111 patients who fulfilled inclusion/exclusion criteria were screened for anxiety and depression with help of Aga Khan University Anxiety and Depression Scale (AKUADS). The data was entered and analyzed by Statistical Package for Social Sciences (Version 10.0).Results: The population consisted mainly of middle aged (mean age 41) females (80.2%). The most …

Gαq And Its AktIons, David M. Harris, Andrea D. Eckhart, Walter J. Koch

Department of Medicine Faculty Papers

No abstract available.

Secondary N-Nitrosocarbamate Anions: Structure And Alkylation Reactions. A Dft Study, Vladimir Benin

Chemistry Faculty Publications

The current article reports theoretical studies (DFT: B3LYP/6-31+G(d)) on the structure and alkylation reactions of the anions of some secondary N-nitrosocarbamates, a class of ambident nucleophiles whose chemistry has been little explored. Several anions (1–4), with an increasing size of the carbamate alkyl (aryl) group were investigated, in an attempt to establish the influence of the size of that group on the thermal stability and regioselectivity of alkylation of the title anions. The conclusion is that thermal stability and the mode of reaction are affected significantly only in the presence of very large and branched carbamate groups. The thermal …

Staphylococcus Aureus Escapes More Efficiently From The Phagosome Of A Cystic Fibrosis Bronchial Epithelial Cell Line Than From Its Normal Counterpart, Todd M. Jarry, Ambrose L. Cheung

Dartmouth Scholarship

Staphylococcus aureus is frequently the initial bacterium isolated from young cystic fibrosis (CF) patients, and yet its role in CF disease progression has not been determined. Recent data from our lab demonstrates that S. aureus can invade and replicate within the CF tracheal epithelial cell line (CFT-1). Here we describe the finding that the fate of internalized S. aureus in CFT-1 cells differs from its complemented counterpart (LCFSN). S. aureus strain RN6390 was able to replicate within the mutant CFT-1 cells after invasion but not in the complemented LCFSN cells. At 1 h postinvasion, S. aureus containing vesicles within both …

Genetic Networks Modulating Retinal Injury, Felix Vazquez-Chona

Theses and Dissertations (ETD)

Many advances have and are being made with the advent of modern sciences. One area that remains resistant to significant advances is the recovery of the mammalian central nervous system (CNS) after injury. Considerable efforts were placed on understanding the cellular and biochemical changes occurring after injury and during wound healing. Aside from cataloging the changes that occur, little progress is being made in understanding the molecular cascades associated with the control of the healing process. The present series of studies define the global changes that occur after injury. They also define CNS repair mechanisms by identifying genetic networks that …

The Vaccinia-Related Kinases Phosphorylate The N' Terminus Of Baf, Regulating Its Interaction With Dna And Its Retention In The Nucleus, R. Jeremy Nichols, Matthew S. Wiebe, Paula Traktman

Nebraska Center for Virology: Faculty Publications

The vaccinia-related kinases (VRKs) comprise a branch of the casein kinase family whose members are characterized by homology to the vaccinia virus B1 kinase. The VRK orthologues encoded by Caenorhabditis elegans and Drosophila melanogaster play an essential role in cell division; however, substrates that mediate this role have yet to be elucidated. VRK1 can complement the temperature sensitivity of a vaccinia B1 mutant, implying that VRK1 and B1 have overlapping substrate specificity. Herein, we demonstrate that B1, VRK1, and VRK2 efficiently phosphorylate the extreme N' terminus of the BAF protein (Barrier to Autointegration Factor). BAF binds to both DNA and …

Mixed Germ Cell Sex Cord-Stromal Tumors Of The Testis And Ovary. Morphological, Immunohistochemical, And Molecular Genetic Study Of Seven Cases, Michal Michal, Tomas Vanacek, Radek Sima, Petr Mukensnabl, Ondrej Hes, Dmitry V. Kazakov, Jozef Matoska, Anna Zuntova, Vladimir Dvorak, Alexander Talerman

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

We present the morphological, immunohistochemical, and molecular genetic features of three cases of testicular and four cases of ovarian mixed germ cell sex cord-stromal tumors (MGSCT). The germ cells in the testicular MGSCTs morphologically differed from those in classical seminomas by lacking the typical "square off" quality of the nuclei. In contrast to the nuclei in classical seminomas, their size in testicular MGSCTs was smaller and nucleoli were inconspicuous and the cytoplasm was Periodic Acid-Schiff(PAS) negative. Quite on the contrary, the variability in the size of the nuclei of the germ cells in the testicular MGSCTs was more similar to …

The Molecular Portraits Of Breast Tumors Are Conserved Acress Microarray Platforms, Zhiyuan Hu, Cheng Fan, Daniel S. Oh, J. S. Marron, Xiaping He, Bahjat F. Qaqish, Chad Livasy, Lisa A. Carey, Evangeline Reynolds, Lynn Dressler, Andrew Nobel, Joel Parker, Matthew G. Ewend, Lynda R. Sawyer, Junyuan Wu, Yudong Liu, Rita Nanda, Maria Tretiakova, Alejandra Ruiz Orrico, Donna Dreher, Juan P. Palazzo, Laurent Perreard, Edward Nelson, Mary Mone, Heidi Hansen, Michael Mullins, John F. Quackenbush, Matthew J. Ellis, Olufunmilayo I. Olopade, Philip S. Bernard, Charles M. Perou

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background

Validation of a novel gene expression signature in independent data sets is a critical step in the development of a clinically useful test for cancer patient risk-stratification. However, validation is often unconvincing because the size of the test set is typically small. To overcome this problem we used publicly available breast cancer gene expression data sets and a novel approach to data fusion, in order to validate a new breast tumor intrinsic list.

Results

A 105-tumor training set containing 26 sample pairs was used to derive a new breast tumor intrinsic gene list. This intrinsic list contained 1300 genes …

Lack Of Il-15 Results In The Suboptimal Priming Of Cd4+ T Cell Response Against An Intracellular Parasite, Crescent L. Combe, Magali M. Moretto, Joseph D. Schwartzman, Jason P. Gigley, David J. Bzik, Imtiaz A. Khan

Dartmouth Scholarship

IFN-gamma-producing CD4+ T cells, although important for protection against acute Toxoplasma gondii infection, can cause gut pathology, which may prove to be detrimental for host survival. Here we show that mice lacking IL-15 gene develop a down-regulated IFN-gamma-producing CD4+ T cell response against the parasite, which leads to a reduction in gut necrosis and increased level of survival against infection. Moreover, transfer of immune CD4+ T cells from WT to IL-15-/- mice reversed inhibition of gut pathology and caused mortality equivalent to levels of parental WT mice. Down-regulated CD4+ T cell response in the absence of IL-15, manifested as reduced …

Scientific Issues Related To The Cytology Proficiency Testing Regulations, George Birdsong, Lydia Howell, Karen Atkinson, R. Marshall Austin, Marluce Bibbo, Thomas A. Bonfiglio, Diane D. Davey, Catherine Keebler, Dina Mody, Lynnette Savaloja, Jacalyn Papillo, Marianne Prey, Stephen Raab, Brenda L. Schultz, Diane Solomon

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The member organizations of the Cytology Education and Technology Consortium believe there are significant flaws in current cytology proficiency testing regulations. The most immediate needed modifications include lengthening the required testing interval, utilizing stringently validated and continuously monitored slides, changing the grading scheme, and changing the focus of the test from the individual to laboratory level testing. Integration of new computer-assisted and located-guided screening technologies into the testing protocols is necessary for the testing protocol to be compliant with the law.

Self-Appraisal Decisions Evoke Dissociated Dorsal-Ventral Ampfc Networks, Taylor W. Schmitz, Sterling C. Johnson

Brain and Mind Institute Researchers' Publications

The anterior medial prefrontal cortex (aMPFC) is consistently active during personally salient decisions, yet the differential contributory processes of this region along the dorsal-ventral axis are less understood. Using a self-appraisal decision-making task and functional magnetic resonance imaging, we demonstrated task-dependent connectivity of ventral aMPFC with amygdala, insula, and nucleus accumbens, and dorsal aMPFC connectivity with dorsolateral PFC and bilateral hippocampus. These aMPFC networks appear to subserve distinct contributory processes inherent to self-appraisal decisions, specifically a dorsally mediated cognitive and a ventrally mediated affective/self-relevance network. © 2005 Elsevier Inc. All rights reserved.

Cardiac-Specific Elevations In Thyroid Hormone Enhance Contractility And Prevent Pressure Overload-Induced Cardiac Dysfunction, Maria G. Trivieri, Gavin Y. Oudit, Rajan Sah, Benoit-Giles Kerfant, Hui Sun, Anthony O. Gramolini, Yan Pan, Alan D. Wickenden, Walburga Croteau

Dartmouth Scholarship

Thyroid hormone (TH) is critical for cardiac development and heart function. In heart disease, TH metabolism is abnormal, and many biochemical and functional alterations mirror hypothyroidism. Although TH therapy has been advocated for treating heart disease, a clear benefit of TH has yet to be established, possibly because of peripheral actions of TH. To assess the potential efficacy of TH in treating heart disease, type 2 deiodinase (D2), which converts the prohormone thyroxine to active triiodothyronine (T3), was expressed transiently in mouse hearts by using the tetracycline transactivator system. Increased cardiac D2 activity led to elevated cardiac T3 levels and …

Heme Deficiency In Alzheimer's Disease: A Possible Connection To Porphyria, Barney E. Dwyer, Meghan L. Stone, Xiongwei Zhu, George Perry, Mark A. Smith

Dartmouth Scholarship

Mechanisms that cause Alzheimer's disease (AD), an invariably fatal neurodegenerative disease, are unknown. Important recent data indicate that neuronal heme deficiency may contribute to AD pathogenesis. If true, factors that contribute to the intracellular heme deficiency could potentially alter the course of AD. The porphyrias are metabolic disorders characterized by enzyme deficiencies in the heme biosynthetic pathway. We hypothesize that AD may differ significantly in individuals possessing the genetic trait for an acute hepatic porphyria. We elaborate on this hypothesis and briefly review the characteristics of the acute hepatic porphyrias that may be relevant to AD. We note the proximity …

Metaplastic Carcinoma Of The Breast, An Intriguing Rarity., Naila Kayani, Fozia Rauf, Yasmin Bhurgri

Department of Pathology and Laboratory Medicine

Abstract Metaplastic carcinoma breast is categorized as a rare heterogenous neoplasm generally characterized by a mixtureof adenocarcinoma with dominant areas of spindle cell, squamous and/or other mesenchymal differentiation. Todetermine the epidemio-demographic and histopathologic characteristics of this rare entity a retrospective studywas conducted to review all cases at the Aga Khan University Hospital (AKUH) Karachi, received during 1st January2000 to 31st August 2005. Twenty-four patients were identified with a mean age at diagnosis of 46.4 (±SD 3.8) years,and an age range of 28-68 years. The mean tumor size was 7.9 cm, range 2.0–17.0 cms (±SD 4.77). The specimenswere mostly obtained by …

Phylloides Tumors In Adolescent Girls And Young Women In Pakistan., Naila Kayani, Amna Khurshid, Yasmin Bhurgri

Department of Pathology and Laboratory Medicine

Abstract The objective of this study was to determine the frequency of phylloides tumor (PT) in adolescent girls and youngwomen (less than and equal to 25 years of age) and to define the clinico-pathological features of PT in this unusualclinical setting. This descriptive study was carried out at the Aga Khan University Hospital (AKUH) pathologydepartment. All consecutive cases of PT diagnosed during the last sixteen years in the section of histopathology from1st January 1990 to 31st June 2005 were included. Selection of cases was restricted to patients up to 25 years of age.A total of 42 cases of PT in …

Pro-Opiomelanocortin Co-Localizes With Corticotropin-Releasing Factor In Axon Terminals Of The Noradrenergic Nucleus Locus Coeruleus, Beverly A.S. Reyes, Julia D. Glaser, Ronaldo Magtoto, Elisabeth K. Van Bockstaele

Department of Neurosurgery Faculty Papers

We previously demonstrated that the opioid peptide, enkephalin, and corticotropin-releasing factor (CRF) are occasionally co-localized in individual axon terminals but more frequently converge on common dendrites in the locus coeruleus (LC). To further examine potential opioid co-transmitters in CRF afferents, we investigated the distribution of proopiomelanocortin (POMC), the precursor that yields the potent bioactive peptide, ß-endorphin, with respect to CRF immunoreactivity using immunofluorescence and immunoelectron microscopic analyses of the LC. Coronal sections were collected through the dorsal pontine tegmentum of rat brain and processed for immunocytochemical detection of POMC and CRF or tyrosine hydroxylase (TH). POMC-immunoreactive processes exhibited a distinct …

Fibrinogen-Containing Y Chains; Is The Assay Measuring What Farrell's Group Expects?, Kevin R. Siebenlist

Biomedical Sciences Faculty Research and Publications

No abstract provided.

Voltage-Dependent Gating Rearrangements In The Intracellular T1-T1 Interface Of A K+ Channel., Guangyu Wang, Manuel Covarrubias

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The intracellular tetramerization domain (T1) of most eukaryotic voltage-gated potassium channels (Kv channels) exists as a "hanging gondola" below the transmembrane regions that directly control activation gating via the electromechanical coupling between the S4 voltage sensor and the main S6 gate. However, much less is known about the putative contribution of the T1 domain to Kv channel gating. This possibility is mechanistically intriguing because the T1-S1 linker connects the T1 domain to the voltage-sensing domain. Previously, we demonstrated that thiol-specific reagents inhibit Kv4.1 channels by reacting in a state-dependent manner with native Zn(2+) site thiolate groups in the T1-T1 interface; …

Animal Carcinogenicity Studies: Implications For The Reach System, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Experimentation Collection

The 2001 European Commission proposal for the Registration, Evaluation and Authorisation of Chemicals (REACH) aims to improve public and environmental health by assessing the toxicity of, and restricting exposure to, potentially toxic chemicals. The greatest benefits are expected to accrue from decreased cancer incidences. Hence the accurate identification of chemical carcinogens must be a top priority for the REACH system. Due to a paucity of human clinical data, the identification of potential human carcinogens has conventionally relied on animal tests. However, our survey of the US Environmental Protection Agency’s (EPA’s) toxic chemicals database revealed that, for a majority of the …

Numerical Distribution Of Lymphoid Nodules In The Human Sigmoid Colon, Rectosigmoidal Junction, Rectum, And Anal Canal, Ivan L. Cameron, James E. Kent, Ron Philo, Christopher J. Barnes, W. Elaine Hardman

Biochemistry and Microbiology

There is little information on the numerical distribution of lymphoid nodules (LN) in distal segments of the human large bowel. A novel approach was therefore developed to assess the number of LN in the sigmoid colon, the rectosigmoid segment, the rectum, and the anal canal in humans. The distal large bowel from five cadavers was selected for quantitative study. The number of LN was scored macroscopically from the proximal sigmoid colon to the distal anal canal. A numerical distribution, previously unreported, consisting of two circular bands of LN was observed in each of the five cadavers. One band was located …

Follicular Dendritic Cell Sarcoma Of Lymph Node - A Rare Entity, Safoorah Khalid, Nausheen Yaqoob, Shahid Pervez

Department of Pathology and Laboratory Medicine

Follicular dendritic cells (FDC) are non-lymphoid, non-phagocytic accessory cells in the immune system that are essential for antigen presentation and germinal center reaction regulation1. These cells are CD21+, CD35+, CD1a- and S100 protein + and they show desmosomes ultrastructurally.

The most commonly involved sites by FDC tumors are lymph nodes but may arise at a variety of extranodal sites including oral cavity, tonsil, gastrointestinal tract and liver. Most studies represent single case reports or case series.

Our patient presented with tumor in the lymph nodes. Histology revealed tumor cells with abundant eosinophilic cytoplasm, hyperchromatic and pleomorphic nuclei, and prominent nucleoli. …

The Ribosome-Recycling Step: Consensus Or Controversy?, Go Hirokawa, Natalia Demeshkina, Nobuhiro Iwakura, Hideko Kaji, Akira Kaji

Department of Biochemistry and Molecular Biology Faculty Papers

Ribosome recycling, the last step in translation, is now accepted as an essential process for prokaryotes. In 2005, three laboratories showed that ribosome-recycling factor (RRF) and elongation factor G (EF-G) cause dissociation of ribosomes into subunits, solving the long-standing problem of how this essential step of translation occurs. However, there remains ongoing controversy regarding the other actions of RRF and EF-G during ribosome recycling. We propose that the available data are consistent with the notion that RRF and EF-G not only split ribosomes into subunits but also participate directly in the release of deacylated tRNA and mRNA for the next …

Hepatic And Renal Cytochrome P450 Gene Regulation During Citrobacter Rodentium Infection In Wild-Type And Toll-Like Receptor 4 Mutant Mice, Terrilyn A Richardson, Melanie Sherman, Leposava Antonovic, Sean S Kardar, Henry W Strobel, Daniel Kalman, Edward T Morgan

Faculty, Staff and Student Publications

Citrobacter rodentium is the rodent equivalent of human enteropathogenic Escherichia coli infection. This study investigated regulation of hepatic and renal cytochrome P450 (P450) mRNAs, hepatic P450 proteins, cytokines, and acute phase proteins during C. rodentium infection. Female C3H/HeOuJ (HeOu) and C3H/HeJ (HeJ) mice [which lack functional toll-like receptor 4 (TLR4)] were infected with C. rodentium by oral gavage and sacrificed 6 days later. Hepatic CYP4A10 and 4A14 mRNAs were decreased in HeOu mice (

Cell-Signalling Dynamics In Time And Space, Boris N. Kholodenko Phd, Dsci

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The specificity of cellular responses to receptor stimulation is encoded by the spatial and temporal dynamics of downstream signalling networks. Computational models provide insights into the intricate relationships between stimuli and responses and reveal mechanisms that enable networks to amplify signals, reduce noise and generate discontinuous bistable dynamics or oscillations. These temporal dynamics are coupled to precipitous spatial gradients of signalling activities, which guide pivotal intracellular processes, but also necessitate mechanisms to facilitate signal propagation across a cell.

Trading The Micro-World Of Combinatorial Complexity For The Macro-World Of Protein Interaction Domains, Nikolay M. Borisov, Nick I. Markevitch, Jan B. Hoek, Boris N. Kholodenko

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Membrane receptors and proteins involved in signal transduction display numerous binding domains and operate as molecular scaffolds generating a variety of parallel reactions and protein complexes. The resulting combinatorial explosion of the number of feasible chemical species and, hence, different states of a network greatly impedes mechanistic modeling of signaling systems. Here we present novel general principles and identify kinetic requirements that allow us to replace a mechanistic picture of all possible micro-states and transitions by a macro-description of states of separate binding sites of network proteins. This domain-oriented approach dramatically reduces computational models of cellular signaling networks by dissecting …

Length-Dependent Degradation Of Single-Stranded 3' Ends By The Werner Syndrome Protein (Wrn): Implications For Spatial Orientation And Coordinated 3' To 5' Movement Of Its Atpase/Helicase And Exonuclease Domains, Amrita Machwe, Liren Xiao, David K. Orren

Toxicology and Cancer Biology Faculty Publications

BACKGROUND: The cancer-prone and accelerated aging disease Werner syndrome is caused by loss of function of the WRN gene product that possesses ATPase, 3' to 5' helicase and 3' to 5' exonuclease activities. Although WRN has been most prominently suggested to function in telomere maintenance, resolution of replication blockage and/or recombinational repair, its exact role in DNA metabolism remains unclear. WRN is the only human RecQ family member to possess both helicase and exonuclease activity, but the mechanistic relationship between these activities is unknown. In this study, model single-stranded and 3' overhang DNA substrates of varying length and structure were …

Lung Development In Laminin Γ2 Deficiency: Abnormal Tracheal Hemidesmosomes With Normal Branching Morphogenesis And Epithelial Differentiation, Nguyet M. Nguyen, Leena Pulkkinen, Jessica A. Schlueter, Guerrino Meneguzzi, Jouni Uitto, Robert M. Senior

Department of Dermatology and Cutaneous Biology Faculty Papers

Background

Laminin γ2 (Lamc2), one of the polypeptides in laminin-332 (laminin-5), is prominent in the basement membrane of alveolar walls and airways of developing and adult lung. Laminins are important for lung morphogenesis and based on its localization, a function for laminin γ2 in lung development has been hypothesized. Targeted deletion of the laminin γ2 gene in mice results in skin blistering and neonatal death at 3–5 days after birth due to failure to thrive.

Methods

Examination of lung development in Lamc2-/- mice through 1–2 days postnatal was accomplished by morphometric analysis, lung bud culture, electron microscopy, immunohistochemical …